Skip Navigation
Skip to contents

Cancer Res Treat : Cancer Research and Treatment

OPEN ACCESS

Search

Page Path
HOME > Search
2 "MicroRNAs"
Filter
Filter
Article category
Keywords
Publication year
Authors
Funded articles
Original Articles
Upregulation of MicroRNA-1246 Is Associated with BRAF Inhibitor Resistance in Melanoma Cells with Mutant BRAF
Jae-Hyeon Kim, Jun-Ho Ahn, Michael Lee
Cancer Res Treat. 2017;49(4):947-959.   Published online January 3, 2017
DOI: https://doi.org/10.4143/crt.2016.280
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Intrinsic and acquired resistance limit the therapeutic benefits of inhibitors of oncogenic BRAF in melanoma. To identify microRNAs (miRNAs) associated with resistance to a BRAF inhibitor, we compared miRNA expression levels in three cell lines with different BRAF inhibitor sensitivity.
Materials and Methods
miRNA microarray analysis was conducted to compare miRNA expression levels. Real-time quantitative reverse-transcription polymerase chain reaction (qRT-PCR) was performed to confirm the expression of differentially expressed miRNAs. The cellular effects of miR-1246 were further examined by MTT assay, immunoblotting analysis, cell cycle analysis, flow cytometric assay of apoptosis, and autophagy assay.
Results
The miRNA microarray analysis and qRT-PCR identified five miRNAs (miR-3617, miR-92a-1, miR-1246, miR-193b-3p, and miR-17-3p) with expression that was consistently altered in two BRAF inhibitor-resistant cell lines. Among the five miRNAs, a miR-1246 mimic significantly reduced the antiproliferative effects of the BRAF inhibitor PLX4720 in BRAF inhibitor–resistant A375P (A375P/Mdr) cells, suggesting that miR-1246 upregulation confers acquired resistance to BRAF inhibition. In particular, apoptosis was identified as a major type of cell death in miR-1246–transfected cells; however, necrosis predominated in mimic-control-transfected cells, indicating that the resistance to PLX4720 in miR-1246 mimic-transfected cells is predominantly due to a reduction in necrosis. Furthermore, we found that miR-1246 promoted G2/M arrest through autophagy as a way to escape cell death by necrosis and apoptosis in response to PLX4720. The promotion of BRAF inhibitor resistance by miR-1246 was associated with lowered levels of p-ERK.
Conclusion
These results suggest that miR-1246 may be a potential therapeutic target in melanoma with acquired resistance to BRAF inhibitors.

Citations

Citations to this article as recorded by  
  • Non-coding RNAs in BRAF-mutant melanoma: targets, indicators, and therapeutic potential
    S. Afsar, Rahamat Unissa Syed, Weam M. A. Khojali, Najat Masood, Mhdia Elhadi Osman, J. Siva Jyothi, Mohd. Abdul Hadi, Amna Abakar Suleiman Khalifa, Nayla Ahmed Mohammed Aboshouk, Hessa Ahmed Alsaikhan, Aljuri Saleh Alafnan, Bushra Abdullah Alrashidi
    Naunyn-Schmiedeberg's Archives of Pharmacology.2025; 398(1): 297.     CrossRef
  • The role of non-coding RNAs in the regulation of cell death pathways in melanoma
    Yekta Metanat, Maria Sviridova, Bareq N. Al-Nuaimi, Fateme Janbazi, Mahtab Jalali, Nogol Ghalamkarpour, Elnaz Khodabandehloo, Ehsan Ahmadi
    Discover Oncology.2025;[Epub]     CrossRef
  • Establishment of Initiated Cell Line Derived From NIH3T3 Fibroblasts
    Myeong‐Han Ro, Taehyun Park, SungHee Hwang, Hye‐Gyo Kim, Michael Lee, Misu Lee
    IUBMB Life.2025;[Epub]     CrossRef
  • Tumor microenvironment responded naturally extracted FOF1-ATPase loaded chromatophores for antitumor therapy
    Weiyong Hong, Bang Lou, Ying Gao, Hui Zhao, Sanjun Ying, Saicheng Yang, Hanbing Li, Qingliang Yang, Gensheng Yang
    International Journal of Biological Macromolecules.2023; 230: 123127.     CrossRef
  • MITF Downregulation Induces Death in Human Mast Cell Leukemia Cells and Impairs IgE-Dependent Degranulation
    Elizabeth Proaño-Pérez, Laia Ollé, Yanru Guo, Cristina Aparicio, Mario Guerrero, Rosa Muñoz-Cano, Margarita Martin
    International Journal of Molecular Sciences.2023; 24(4): 3515.     CrossRef
  • Autophagy in BRAF-mutant cutaneous melanoma: recent advances and therapeutic perspective
    Elisabetta Fratta, Giorgio Giurato, Roberto Guerrieri, Francesca Colizzi, Jessica Dal Col, Alessandro Weisz, Agostino Steffan, Barbara Montico
    Cell Death Discovery.2023;[Epub]     CrossRef
  • BRAF Mutations in Melanoma: Biological Aspects, Therapeutic Implications, and Circulating Biomarkers
    Giorgia Castellani, Mariachiara Buccarelli, Maria Beatrice Arasi, Stefania Rossi, Maria Elena Pisanu, Maria Bellenghi, Carla Lintas, Claudio Tabolacci
    Cancers.2023; 15(16): 4026.     CrossRef
  • METTL3 promotes Non-Small-Cell Lung Cancer Growth and Metastasis by Inhibiting FDX1 Through Copper Death-Associated Pri-miR-21-5p Maturation
    Shuai Qian, Jun Liu, Wenliang Liao, Fengping Wang
    Epigenomics.2023; 15(23): 1237.     CrossRef
  • A Review on the Role of miR-1246 in the Pathoetiology of Different Cancers
    Soudeh Ghafouri-Fard, Tayyebeh Khoshbakht, Bashdar Mahmud Hussen, Mohammad Taheri, Mohammad Samadian
    Frontiers in Molecular Biosciences.2022;[Epub]     CrossRef
  • Circulating miR-1246 and miR-485-3p as Promising Biomarkers of Clinical Response and Outcome in Melanoma Patients Treated with Targeted Therapy
    Lauretta Levati, Cristian Bassi, Simona Mastroeni, Laura Lupini, Gian Carlo Antonini Cappellini, Laura Bonmassar, Ester Alvino, Simona Caporali, Pedro Miguel Lacal, Maria Grazia Narducci, Ivan Molineris, Federica De Galitiis, Massimo Negrini, Giandomenico
    Cancers.2022; 14(15): 3706.     CrossRef
  • Paradoxical downregulation of LPAR3 exerts tumor-promoting activity through autophagy induction in Ras-transformed cells
    Sung-Hee Hwang, Hye-Gyo Kim, Michael Lee
    BMC Cancer.2022;[Epub]     CrossRef
  • SH3BP2 Silencing Increases miRNAs Targeting ETV1 and Microphthalmia-Associated Transcription Factor, Decreasing the Proliferation of Gastrointestinal Stromal Tumors
    Elizabeth Proaño-Pérez, Eva Serrano-Candelas, Cindy Mancia, Arnau Navinés-Ferrer, Mario Guerrero, Margarita Martin
    Cancers.2022; 14(24): 6198.     CrossRef
  • Carfilzomib in Combination with Bortezomib Enhances Apoptotic Cell Death in B16-F1 Melanoma Cells
    Min Seung Lee, So Hyun Lim, Ah-Ran Yu, Chi Yeon Hwang, Insug Kang, Eui-Ju Yeo
    Biology.2021; 10(2): 153.     CrossRef
  • Resistance to Molecularly Targeted Therapies in Melanoma
    Meet Patel, Adam Eckburg, Shahina Gantiwala, Zachary Hart, Joshua Dein, Katie Lam, Neelu Puri
    Cancers.2021; 13(5): 1115.     CrossRef
  • Learning from Embryogenesis—A Comparative Expression Analysis in Melanoblast Differentiation and Tumorigenesis Reveals miRNAs Driving Melanoma Development
    Lisa Linck-Paulus, Lisa Lämmerhirt, Daniel Völler, Katharina Meyer, Julia C. Engelmann, Rainer Spang, Norbert Eichner, Gunter Meister, Silke Kuphal, Anja Katrin Bosserhoff
    Journal of Clinical Medicine.2021; 10(11): 2259.     CrossRef
  • METTL3 promotes the initiation and metastasis of ovarian cancer by inhibiting CCNG2 expression via promoting the maturation of pri-microRNA-1246
    Xuehan Bi, Xiao Lv, Dajiang Liu, Hongtao Guo, Guang Yao, Lijuan Wang, Xiaolei Liang, Yongxiu Yang
    Cell Death Discovery.2021;[Epub]     CrossRef
  • Choosing The Right Animal Model for Renal Cancer Research
    Paweł Sobczuk, Anna Brodziak, Mohammed Imran Khan, Stuti Chhabra, Michał Fiedorowicz, Marlena Wełniak-Kamińska, Kamil Synoradzki, Ewa Bartnik, Agnieszka Cudnoch-Jędrzejewska, Anna M. Czarnecka
    Translational Oncology.2020; 13(3): 100745.     CrossRef
  • Circulating microRNAs as biomarkers for early diagnosis of cutaneous melanoma
    Sara Carpi, Beatrice Polini, Stefano Fogli, Adriano Podestà, Erkko Ylösmäki, Vincenzo Cerullo, Antonella Romanini, Paola Nieri
    Expert Review of Molecular Diagnostics.2020; 20(1): 19.     CrossRef
  • Autophagy inhibition in 3T3-L1 adipocytes breaks the crosstalk with tumor cells by suppression of adipokine production
    Sung-Hee Hwang, Michael Lee
    Animal Cells and Systems.2020; 24(1): 17.     CrossRef
  • Roles of S100 family members in drug resistance in tumors: Status and prospects
    Xin Hua, Hongming Zhang, Jinfang Jia, Shanshan Chen, Yue Sun, Xiaoli Zhu
    Biomedicine & Pharmacotherapy.2020; 127: 110156.     CrossRef
  • MicroRNAs as Key Players in Melanoma Cell Resistance to MAPK and Immune Checkpoint Inhibitors
    Maria Letizia Motti, Michele Minopoli, Gioconda Di Carluccio, Paolo Antonio Ascierto, Maria Vincenza Carriero
    International Journal of Molecular Sciences.2020; 21(12): 4544.     CrossRef
  • Circulating miRNAs in Small Extracellular Vesicles Secreted by a Human Melanoma Xenograft in Mouse Brains
    Loredana Guglielmi, Marta Nardella, Carla Musa, Ingrid Cifola, Manuela Porru, Beatrice Cardinali, Ilaria Iannetti, Chiara Di Pietro, Giulia Bolasco, Valentina Palmieri, Laura Vilardo, Nicolò Panini, Fabrizio Bonaventura, Massimiliano Papi, Ferdinando Scav
    Cancers.2020; 12(6): 1635.     CrossRef
  • MiR‐1246 promotes anti‐apoptotic effect of mini‐αA in oxidative stress‐induced apoptosis in retinal pigment epithelial cells
    Qianyin Chen, Huimin Lin, Xuan Deng, Shengnan Li, Jinglin Zhang
    Clinical & Experimental Ophthalmology.2020; 48(5): 682.     CrossRef
  • Mechanisms of Acquired BRAF Inhibitor Resistance in Melanoma: A Systematic Review
    Ilaria Proietti, Nevena Skroza, Nicoletta Bernardini, Ersilia Tolino, Veronica Balduzzi, Anna Marchesiello, Simone Michelini, Salvatore Volpe, Alessandra Mambrin, Giorgio Mangino, Giovanna Romeo, Patrizia Maddalena, Catherine Rees, Concetta Potenza
    Cancers.2020; 12(10): 2801.     CrossRef
  • The potential of BRAF-associated non-coding RNA as a therapeutic target in melanoma
    Luigi Fattore, Rita Mancini, Paolo Antonio Ascierto, Gennaro Ciliberto
    Expert Opinion on Therapeutic Targets.2019; 23(1): 53.     CrossRef
  • A plasma microRNA biomarker of melanoma as a personalised assessment of treatment response
    Ryan K. van Laar, Mitchel T. Lincoln, Barton J. van Laar
    Melanoma Research.2019; 29(1): 19.     CrossRef
  • A three plasma microRNA signature for papillary thyroid carcinoma diagnosis in Chinese patients
    Zhiyan Wang, Jinru Lv, Xuan Zou, Zebo Huang, Huo Zhang, Qingxie Liu, Lin Jiang, Xin Zhou, Wei Zhu
    Gene.2019; 693: 37.     CrossRef
  • The origin of exosomal miR-1246 in human cancer cells
    Yi-Fan Xu, Bethany N. Hannafon, Ujjwol Khatri, Amy Gin, Wei-Qun Ding
    RNA Biology.2019; 16(6): 770.     CrossRef
  • Differential Gene Expression Common to Acquired and Intrinsic Resistance to BRAF Inhibitor Revealed by RNA-Seq Analysis
    Jun-Ho Ahn, Sung-Hee Hwang, Hyun-Soo Cho, Michael Lee
    Biomolecules & Therapeutics.2019; 27(3): 302.     CrossRef
  • MicroRNA heterogeneity in melanoma progression
    Anita Thyagarajan, Kenneth Y. Tsai, Ravi P. Sahu
    Seminars in Cancer Biology.2019; 59: 208.     CrossRef
  • miR-126-3p down-regulation contributes to dabrafenib acquired resistance in melanoma by up-regulating ADAM9 and VEGF-A
    Simona Caporali, Adriana Amaro, Lauretta Levati, Ester Alvino, Pedro Miguel Lacal, Simona Mastroeni, Federica Ruffini, Laura Bonmassar, Gian Carlo Antonini Cappellini, Nadia Felli, Alessandra Carè, Ulrich Pfeffer, Stefania D’Atri
    Journal of Experimental & Clinical Cancer Research.2019;[Epub]     CrossRef
  • MicroRNA-1246 regulates the radio-sensitizing effect of curcumin in bladder cancer cells via activating P53
    Ran Xu, Huabing Li, Shuiqing Wu, Jian Qu, Haiyan Yuan, Yangang Zhou, Qiong Lu
    International Urology and Nephrology.2019; 51(10): 1771.     CrossRef
  • The “-OMICS” facet of melanoma: Heterogeneity of genomic, proteomic and metabolomic biomarkers
    Douglas Donnelly, Phyu P. Aung, George Jour
    Seminars in Cancer Biology.2019; 59: 165.     CrossRef
  • Upregulation of S100A9 contributes to the acquired resistance to BRAF inhibitors
    Sung-Hee Hwang, Jun-Ho Ahn, Michael Lee
    Genes & Genomics.2019; 41(11): 1273.     CrossRef
  • Targeting CDC7 sensitizes resistance melanoma cells to BRAFV600E-specific inhibitor by blocking the CDC7/MCM2-7 pathway
    Shaimaa A. Gad, Hamdy E. A. Ali, Rofaida Gaballa, Rania M. Abdelsalam, Mourad Zerfaoui, Hamed I. Ali, Salwa H. Salama, Sanaa A. Kenawy, Emad Kandil, Zakaria Y. Abd Elmageed
    Scientific Reports.2019;[Epub]     CrossRef
  • The Role of Autophagy in the Resistance to BRAF Inhibition in BRAF-Mutated Melanoma
    Xiao Liu, Jinfeng Wu, Haihong Qin, Jinhua Xu
    Targeted Oncology.2018; 13(4): 437.     CrossRef
  • Targeting signal-transducer-and-activator-of-transcription 3 sensitizes human cutaneous melanoma cells to BRAF inhibitor
    Xiaohui Wang, Huajun Qu, Yinghe Dong, Guozhi Wang, Yuchen Zhen, Linxia Zhang
    Cancer Biomarkers.2018; 23(1): 67.     CrossRef
  • Exosome-packaged miR-1246 contributes to bystander DNA damage by targeting LIG4
    Li-Jun Mo, Man Song, Qiao-Hua Huang, Hua Guan, Xiao-Dan Liu, Da-Fei Xie, Bo Huang, Rui-Xue Huang, Ping-Kun Zhou
    British Journal of Cancer.2018; 119(4): 492.     CrossRef
  • An oasis in the desert of cancer chemotherapeutic resistance: The enlightenment from reciprocal crosstalk between signaling pathways of UPR and autophagy in cancers
    Yuhang Zhang, Xianjun Qu, Lingfan Jiang
    Biomedicine & Pharmacotherapy.2017; 92: 972.     CrossRef
  • 14,735 View
  • 399 Download
  • 40 Web of Science
  • 39 Crossref
Close layer
Gastric Carcinogenesis in the miR-222/221 Transgenic Mouse Model
Boram Choi, Jieun Yu, Tae-Su Han, Young-Kook Kim, Keun Hur, Byeong-Cheol Kang, Woo-Ho Kim, Dae-Yong Kim, Hyuk-Joon Lee, V. Narry Kim, Han-Kwang Yang
Cancer Res Treat. 2017;49(1):150-160.   Published online June 23, 2016
DOI: https://doi.org/10.4143/crt.2015.462
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
MicroRNAs (miRNAs) regulate various cellular functions, including development, cell proliferation, apoptosis, and tumorigenesis. Different signatures associated with various tissue types, diagnosis, progression, prognosis, staging, and treatment response have been identified by miRNA expression profiling of human tumors. miRNAs function as oncogenes or as tumor suppressors. The relationship between gastric cancer and miRNA garnered attention due to the high incidence of gastric cancer in Asian countries. miR-222/221 expression increases in gastric tumor tissues. The oncogenic effect of miR-222/221 was previously determined in functional studies and xenograft models. In this study, transgenic mice overexpressing miR-222/221 were generated to confirm the effect of miR-222/221 on gastric carcinogenesis. Materials and Methods At 6 weeks of age, 65 transgenic mice and 53 wild-type mice were given drinking water containing N-nitroso-N-methylurea (MNU) for 5 alternating weeks to induce gastric cancer. The mice were euthanized at 36 weeks of age and histologic analysis was performed.
Results
Hyperplasia was observed in 3.77% of the wild-type mice and in 18.46% of the transgenic mice (p=0.020). Adenoma was observed in 20.75% of the wild-type mice and 26.15% of the transgenic mice (p=0.522). Carcinoma was observed in 32.08% of the wild-type mice and 41.54% of the transgenic mice (p=0.341). The frequency of hyperplasia, adenoma, and carcinoma was higher in transgenic mice, but the difference was statistically significant only in hyperplasia. Conclusion These results suggest that hyperplasia, a gastric pre-cancerous lesion, is associated with miR-222/221 expression but miR-222/221 expression does not affect tumorigenesis itself.

Citations

Citations to this article as recorded by  
  • Research advancements and evaluation of multifactor‐induced murine models for gastric cancer
    Yiqing Wang, Liang Zhang, Weixu Feng, Wanfeng Liu, Xiangyang Xue, Shiyu Feng
    Animal Models and Experimental Medicine.2025;[Epub]     CrossRef
  • The Mechanism of miR-222 Targets Matrix Metalloproteinase 1 in Regulating Fibroblast Proliferation in Hypertrophic Scars
    Yi Zhang, Wei-Long Hong, Zhi-Ming Li, Qi-Yu Zhang, Kang Zeng
    Aesthetic Plastic Surgery.2021; 45(2): 749.     CrossRef
  • Fraser extracellular matrix complex subunit 1 promotes liver metastasis of gastric cancer
    Shinichi Umeda, Mitsuro Kanda, Takashi Miwa, Haruyoshi Tanaka, Chie Tanaka, Daisuke Kobayashi, Masamichi Hayashi, Suguru Yamada, Goro Nakayama, Masahiko Koike, Yasuhiro Kodera
    International Journal of Cancer.2020; 146(10): 2865.     CrossRef
  • Aldehyde dehydrogenase 1, a target of miR‑222, is expressed at elevated levels in cervical cancer
    Changde Liu, Yan Zhang, Shanghua Liang, Yuhua Ying
    Experimental and Therapeutic Medicine.2020;[Epub]     CrossRef
  • Expression and regulatory role of miRNA-222 in intervertebral disc degeneration (IDD)
    Chen Ge, Changwei Li
    Biotechnology & Biotechnological Equipment.2019; 33(1): 1553.     CrossRef
  • MicroRNA-222 regulates the viability of fibroblasts in hypertrophic scars via matrix metalloproteinase 1
    Yi Zhang, Xiaohua Lin, Li Zhang, Weilong Hong, Kang Zeng
    Experimental and Therapeutic Medicine.2017;[Epub]     CrossRef
  • 15,586 View
  • 299 Download
  • 7 Web of Science
  • 6 Crossref
Close layer

Cancer Res Treat : Cancer Research and Treatment
Close layer
TOP